Synthesis, cellular uptake and animal toxicity of a tetra(carboranylphenyl)-tetrabenzoporphyrin

• Published in: Bioorganic & medicinal chemistry Vol. 14; no. 6; pp. 1871 - 1879
• Main Authors: Gottumukkala, Vijay, Ongayi, Owendi, Baker, David G., Lomax, Larry G., Vicente, M. Graça H.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.03.2006; Elsevier Science
• Subjects: Animals; Biological and medical sciences; BNCT; Boron Compounds - chemical synthesis; Boron Compounds - pharmacokinetics; Boron Compounds - toxicity; Cell Line, Tumor; Cells, Cultured; Drug Screening Assays, Antitumor; Female; Glioblastoma - metabolism; Humans; Male; Medical sciences; Mice; Mice, Inbred BALB C; Molecular Structure; nido-Carborane; PDT; Photoradiation therapy and photosensitizing agent; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - toxicity; Porphyrins - chemical synthesis; Porphyrins - pharmacokinetics; Porphyrins - toxicity; Radiation therapy and radiosensitizing agent; Solubility; Tetrabenzoporphyrin; Treatment with physical agents; Treatment. General aspects; Tumors; Water - chemistry; PDT; BNCT; nido-Carborane; Tetrabenzoporphyrin; Cage compound; Toxicity; Lung; Glioblastoma; Lysosome; V79-Cell line; Female; Oxidation; Chemical synthesis; Boron neutron capture therapy; Tumor cell; Human; Photodynamic therapy; Rodentia; Carborane; Malignant tumor; Neutron therapy; Radiotherapy; In vitro; Biological activity; Uptake; Water soluble compound; Vertebrata; Mammalia; Cell line; Treatment; Mouse; Porphyrin; Animal; Boron Organic compounds; Hamster
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2005.10.037

The total synthesis, cellular uptake, intracellular localization and animal toxicity of a tetra( nido-carboranylphenyl)-tetrabenzoporphyrinporphyrin are described and compared with a known tetra( nido-carboranyl)porphyrin. A water-soluble nido-carboranyl-tetrabenzoporphyrin has been synthesized in 43% overall yield, by condensation of butanopyrrole with a carboranylbenzaldehyde, followed by metal insertion, oxidation, demetallation and deboronation reactions. This compound accumulated within human glioblastoma T98G cells to a significant higher extent than a structurally related nido-carboranylporphyrin, and localized preferentially in the cell lysosomes. Animal toxicity studies using male and female BALB/c mice revealed that both compounds are non-toxic even at a dose of 160 mg/kg, administered intraperitoneally as a single injection at a concentration of 4 mg/mL. It is concluded that the tetra(carboranylphenyl)-tetrabenzoporphyrin is a promising new sensitizer for the treatment of malignant tumors.